The variant did not reduce TNNT1 protein levels or affect its localization but impaired its ability to modulate muscle contraction in response to Ca2+ levels. Identification of the causative variant in TNNT1 finally clarifies that the OCPMD sheep is in fact a large animal model of TNNT1 congenital myopathy. This model could now be used for testing molecular or gene therapies.
  Magnetic resonance imaging (MRI) features are typical findings in Hirayama disease (HD) and are useful diagnostic entities but may not be present in all patients.
 
  We present the case of a 22-year-old Nepalese man who presented with insidious onset of weakness of his right upper limb of more than 5 years duration. His weakness was progressive for the first 3 years, and then remained static. On examination, weakness of the interossei, thenar, hypothenar, flexor, and extensor muscles were present in his right upper limb, power was normal in his left upper and bilateral lower limbs. Minipolymyoclonus was present in both upper limbs, less prominent on the left side. Electrophysiological findings showed motor axonal neuropathy in his right upper limb, neurogenic discharges and fibrillations, and fasciculations in both upper limbs. Contrast magnetic resonance imaging (MRI) of his cervical spine in flexion was normal. Our patient was diagnosed with HD based on clinical and electrophysiological findings. Our patient was advised to use a cervical collar and regular physiotherapy and was found to have subjective benefit.
 
  A normal cervical MRI does not rule out HD and the diagnosis can also be made based on clinical and electrophysiological studies. Progressive distal upper limb weakness or tremor in young patients should be evaluated for HD, because early diagnosis and intervention might halt the progression.
 A normal cervical MRI does not rule out HD and the diagnosis can also be made based on clinical and electrophysiological studies. Progressive distal upper limb weakness or tremor in young patients should be evaluated for HD, because early diagnosis and intervention might halt the progression.Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.
  Instruments for monitoring the clinical status of adolescents with emotional problems are needed. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) according to theory measures problems/symptoms, well-being, functioning and risk. Documentation of whether the theoretical factor structure for CORE-OM is applicable for adolescents is lacking.
 
  This study examined the factor structure and psychometric properties of the CORE-OM based on two samples of adolescents (age 14-18) youths seeking treatment for emotional problems (N = 140) and high school students (N = 531). A split half approach was chosen. An exploratory factor analysis (EFA) was performed on the first half of the stratified samples to establish the suitability of the model. A Confirmatory Factor Analysis (CFA) with the chosen model from the EFA was performed on the second half. Internal consistency and clinical cut-off scores of the CORE-OM were investigated.
 
  The best fitting model only partially confirmed the theoretical model analysis on CORE-OM for adolescents resulted in a five-factor solution, and opens up for new subscales concerning positive resources and problems with others. A 17-item solution for the general problems/symptoms scale is suggested. We advise developers of self-report instruments not to reverse items, if they do not intend to measure a separate factor, since these seem to affect the dimensionality of the scales. Comparing means for gender in non-clinical samples should not be done without modification of the general emotional problem and the positive resources scales. Slightly elevated CORE-OM scores (up to 1.3) in adolescents may be normal fluctuations.
  Metastasectomy is performed on a select cohort of patients with advanced and/or recurrent bone and soft tissue sarcomas because of the potential for long term relapse free and overall survival associated with the procedure. However, the evidence supporting metastasectomy is difficult to summarize without a systematic examination of existing literature. The objective of this systematic review will be to examine survival among both adults and children with advanced and recurrent bone and STS who undergo metastasectomy.
 
  We designed and registered a study protocol for a systematic review and meta-analysis. We will include data from survival studies (e.g., randomized trials, cohort studies, routine case registries, and case control) conducted in children and adults with advanced and recurrent bone and soft tissue sarcoma who undergo metastasectomy. The primary outcome will be overall survival. Secondary outcomes will be 30-day post-operative mortality, recurrence-free survival, time off systemic therapy, and ptify, evaluate, and integrate data on survival of metastasectomy of bone and soft tissue sarcoma by organ of metastasis. Our findings may have implications for clinicians, patients, and their families when considering selection for resection of oligometastatic disease in de novo, or recurrent bone and soft tissue sarcoma.  https://www.selleckchem.com/products/gdc-0994.html  Implications for future research will be identified to improve the outcomes of these complex patients.
 
  PROSPERO CRD42019126906.
 PROSPERO CRD42019126906.